Pin1 protein associates with neuronal lipofuscin: potential consequences in age-related neurodegeneration

Hashemzadeh-Bonehi, Lida, Phillips, Roger Guy, Cairns, Nigel John, Mosaheb, Sabrina and Thorpe, Julian Robert (2006) Pin1 protein associates with neuronal lipofuscin: potential consequences in age-related neurodegeneration. Experimental Neurology, 199 (2). pp. 328-338. ISSN 0014-4886

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Pin1 protein is a peptidyl-prolyl cis-trans isomerase that modulates the activity of a range of proteins involved in cell function. We and others have demonstrated neuronal Pin1 deficits in Alzheimer's disease (AD) and have shown similar deficits in frontotemporal dementia and in aging. Pin1 may, in fact, be a susceptibility factor; others have shown that Pin1 depletion causes apoptosis in HeLa cells. Further, patterns of AD pathology correlate with regions of lower Pin1 expression in normal human brain; Pin1 knockout mice suffer neurodegeneration; and Pin1 can ameliorate p-tau pathology by isomerising p-tau, facilitating its trans-specific dephosphorylation and restoring its ability to bind to and re-stabilise microtubules and thence cytoskeletal integrity. Here, we report a novel localization of high levels of Pin1 with lipofuscin in aging neurons. This association could progressively drain available Pin1 and be deleterious to neuronal function during aging. We also show that Pin1 associates with lipofuscin when lipofuscin accumulations become marked and correlate with susceptibility to neurodegenerative disease. Our data are consistent with the possibility that neuronal Pin1 deficits may be a contributory factor in neurodegeneration associated with aging.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Roger Phillips
Date Deposited: 06 Feb 2012 20:08
Last Modified: 26 Feb 2013 10:01
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